Uncertainty in Premarket Decisions

Medical devices are required to demonstrate a “reasonable” assurance of safety and effectiveness; an “absolute” assurance of safety and effectiveness is not required because there are typically at least some uncertainty concerning the benefits and risks of any given medical device. This uncertainty can be related to the type, magnitude, duration, or frequency of the device’s benefits or risks.

FDA considers several factors when determining the appropriate level of uncertainty for medical devices, including:

The extent of the probable benefits of the device

The extent of the probable risks of the device

The extent of uncertainty regarding the benefit-risk profile of alternative treatments

In the draft guidance, FDA states that it’s “consideration of these factors is intended to be pragmatic, context-dependent (considered in the context of the relevant non-clinical and/or clinical information about the device, e.g., information about the device’s mechanism of action and modes of failure), and consistent with FDA’s statutory and regulatory authorities and requirements.”

Applications & Examples

A greater level of uncertainty may be acceptable for certain types of devices, such as breakthrough devices subject to PMA and devices for small patient populations subject to PMA. Although approval still depends on the totality of valid scientific evidence, the FDA may accept greater uncertainty for devices where probable public health benefits outweigh the probable risks. This is particularly applicable when it is possible to collect additional information in a postmarket setting rather than a premarket setting.

However, according to the draft guidance, “in some cases, resolving or reducing the extent of uncertainty postmarket may not be warranted. For example, the HDE pathway accepts greater uncertainty premarket because the FD&C Act does not require a demonstration of a reasonable assurance of effectiveness; further, the FD&C Act does not require data collection on device effectiveness postmarket.”

Other examples where reducing or resolving uncertainty postmarket may not be necessary include cases where: